Identification of diagnostic markers of pancreatic ductal adenocarcinoma using transcriptomic tumour and blood sample data
Abstract Background Pancreatic ductal adenocarcinoma (PDAC) is the most frequently diagnosed form of pancreatic cancer worldwide. PDAC is associated with a poor survival rate mainly due to the disease being usually diagnosed at late stages. Methods Publicly available gene expression data from 10 stu...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-10-01
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| Series: | Clinical and Translational Discovery |
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| Online Access: | https://doi.org/10.1002/ctd2.248 |
| _version_ | 1797648105826418688 |
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| author | Aristeidis Sionakidis Panagiotis Nikolaos Lalagkas Andigoni Malousi Ioannis S. Vizirianakis |
| author_facet | Aristeidis Sionakidis Panagiotis Nikolaos Lalagkas Andigoni Malousi Ioannis S. Vizirianakis |
| author_sort | Aristeidis Sionakidis |
| collection | DOAJ |
| description | Abstract Background Pancreatic ductal adenocarcinoma (PDAC) is the most frequently diagnosed form of pancreatic cancer worldwide. PDAC is associated with a poor survival rate mainly due to the disease being usually diagnosed at late stages. Methods Publicly available gene expression data from 10 studies with tumour tissue (448 samples) and/or blood samples (128 samples) from PDAC patients were pooled together and analyzed for the identification of stage‐specific and global diagnostic markers using differential gene expression analysis. The list of statistically significant (padj<0.05) differentially expressed genes were used to carry out enrichment analysis via active subnetworks and miRNA enrichment analysis. We then used the results from these analyses to identify the most significant genes and pathways and map these to marketed drugs’ pharmacological targets. The same process was replicated for studies with blood samples and results were compared to those from the tissue analysis. A set of consistently deregulated genes (pancreatic tumour signature, PTS) in both tissue and blood samples was derived and validated in external cohorts and The Cancer Genome Atlas (TCGA) data. Results Notable gene expression deregulation was found in all tumour stages with significant overlap. We identified 820 consistently deregulated genes (PTS) in tissue samples of all stages and blood samples. Active subnetwork analysis revealed enriched ribosome, proteasome, adherens junction and cell cycle pathways across all stages and blood samples. Our findings suggest that microRNA (miRNA) contribution to PDAC pathology plays a significant role and is probably mediated by distinct miRNAs across stages of PDAC. Stage‐specific enriched miRNAs with diagnostic potential included miR‐21, miR‐29, miR‐124 and miR‐30, for stages 1–4, respectively. By investigating the pharmacogenetic interactions of the identified targets with clinically approved drugs, we outline potential paths for personalized interventions. Importantly, the PTS showed a significant association with survival in TCGA data. Conclusion Thus, we present a compilation of protein‐coding markers and miRNAs that hold potential as a diagnostic tool for the early detection of PDAC, as well as for designing novel therapeutic strategies aimed at improving patient outcomes. |
| first_indexed | 2024-03-11T15:27:19Z |
| format | Article |
| id | doaj.art-9831c85ff12441789dc6a3c8b4458ec0 |
| institution | Directory Open Access Journal |
| issn | 2768-0622 |
| language | English |
| last_indexed | 2024-03-11T15:27:19Z |
| publishDate | 2023-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | Clinical and Translational Discovery |
| spelling | doaj.art-9831c85ff12441789dc6a3c8b4458ec02023-10-27T11:42:29ZengWileyClinical and Translational Discovery2768-06222023-10-0135n/an/a10.1002/ctd2.248Identification of diagnostic markers of pancreatic ductal adenocarcinoma using transcriptomic tumour and blood sample dataAristeidis Sionakidis0Panagiotis Nikolaos Lalagkas1Andigoni Malousi2Ioannis S. Vizirianakis3Institute of Genetics and Cancer University of Edinburgh Scotland UKDepartment of Biological Sciences University of Massachusetts Lowell Lowell Massachusetts USALaboratory of Biological Chemistry School of Medicine Aristotle University of Thessaloniki Thessaloniki GreeceLaboratory of Pharmacology School of Pharmacy Aristotle University of Thessaloniki Thessaloniki GreeceAbstract Background Pancreatic ductal adenocarcinoma (PDAC) is the most frequently diagnosed form of pancreatic cancer worldwide. PDAC is associated with a poor survival rate mainly due to the disease being usually diagnosed at late stages. Methods Publicly available gene expression data from 10 studies with tumour tissue (448 samples) and/or blood samples (128 samples) from PDAC patients were pooled together and analyzed for the identification of stage‐specific and global diagnostic markers using differential gene expression analysis. The list of statistically significant (padj<0.05) differentially expressed genes were used to carry out enrichment analysis via active subnetworks and miRNA enrichment analysis. We then used the results from these analyses to identify the most significant genes and pathways and map these to marketed drugs’ pharmacological targets. The same process was replicated for studies with blood samples and results were compared to those from the tissue analysis. A set of consistently deregulated genes (pancreatic tumour signature, PTS) in both tissue and blood samples was derived and validated in external cohorts and The Cancer Genome Atlas (TCGA) data. Results Notable gene expression deregulation was found in all tumour stages with significant overlap. We identified 820 consistently deregulated genes (PTS) in tissue samples of all stages and blood samples. Active subnetwork analysis revealed enriched ribosome, proteasome, adherens junction and cell cycle pathways across all stages and blood samples. Our findings suggest that microRNA (miRNA) contribution to PDAC pathology plays a significant role and is probably mediated by distinct miRNAs across stages of PDAC. Stage‐specific enriched miRNAs with diagnostic potential included miR‐21, miR‐29, miR‐124 and miR‐30, for stages 1–4, respectively. By investigating the pharmacogenetic interactions of the identified targets with clinically approved drugs, we outline potential paths for personalized interventions. Importantly, the PTS showed a significant association with survival in TCGA data. Conclusion Thus, we present a compilation of protein‐coding markers and miRNAs that hold potential as a diagnostic tool for the early detection of PDAC, as well as for designing novel therapeutic strategies aimed at improving patient outcomes.https://doi.org/10.1002/ctd2.248biomarkersdiagnosismicroRNAPDACpharmacogenomicsprecision medicine |
| spellingShingle | Aristeidis Sionakidis Panagiotis Nikolaos Lalagkas Andigoni Malousi Ioannis S. Vizirianakis Identification of diagnostic markers of pancreatic ductal adenocarcinoma using transcriptomic tumour and blood sample data Clinical and Translational Discovery biomarkers diagnosis microRNA PDAC pharmacogenomics precision medicine |
| title | Identification of diagnostic markers of pancreatic ductal adenocarcinoma using transcriptomic tumour and blood sample data |
| title_full | Identification of diagnostic markers of pancreatic ductal adenocarcinoma using transcriptomic tumour and blood sample data |
| title_fullStr | Identification of diagnostic markers of pancreatic ductal adenocarcinoma using transcriptomic tumour and blood sample data |
| title_full_unstemmed | Identification of diagnostic markers of pancreatic ductal adenocarcinoma using transcriptomic tumour and blood sample data |
| title_short | Identification of diagnostic markers of pancreatic ductal adenocarcinoma using transcriptomic tumour and blood sample data |
| title_sort | identification of diagnostic markers of pancreatic ductal adenocarcinoma using transcriptomic tumour and blood sample data |
| topic | biomarkers diagnosis microRNA PDAC pharmacogenomics precision medicine |
| url | https://doi.org/10.1002/ctd2.248 |
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